A multi-center, randomized, double-blind clinical trial to evaluate the safety and tolerability of 24 weeks treatment with vildagliptin (50 mg qd) versus placebo in patients with type 2 diabetes and moderate or severe renal insufficiency

• Register: EUCTR
• Last refreshed on: 15 April 2013
• Main ID: EUCTR2007-003723-21-DE
• Date of registration: 26/09/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multi-center, randomized, double-blind clinical trial to evaluate the safety and tolerability of 24 weeks treatment with vildagliptin (50 mg qd) versus placebo in patients with type 2 diabetes and moderate or severe renal insufficiency
• Scientific title: A multi-center, randomized, double-blind clinical trial to evaluate the safety and tolerability of 24 weeks treatment with vildagliptin (50 mg qd) versus placebo in patients with type 2 diabetes and moderate or severe renal insufficiency
• Date of first enrolment: 18/12/2007
• Target sample size: 525
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003723-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, France, Germany, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age in the range of 18-85 years inclusive at visit 1
2. Patients with T2DM either untreated (defined as not taking anti-diabetic therapy for at least 8 weeks prior to visit 1) or treated with anti-diabetic therapy defined as sulfonylurea, AGIs, TZDs, insulin, and metiglinides as monotherapy or combination therapy for at least 8 weeks prior to visit 1
Patients treated with an AGI can only enter the study if their GFR is = 30 mL/min/1.73 m2; in addition, each country should comply with its local label for the use of AGIs in patients with renal impairment
3. Patients treated with anti-diabetic therapy must be on a stable dose for the past 4 weeks prior to visit 1 (stable insulin therapy is defined as ± 20% of total daily units)
4. GFR of < 50 mL/min/1.73 m2 at visit 1
5. HbA1c of = 6.5 and = 10 % at visit 1
6. Body mass index (BMI) 18-42 kg/m2 at visit 1
7. Male, non-fertile female or female of childbearing potential using a medically approved birth control method by the country health authorities that may include:
- A non-fertile female is defined as: post menopausal (12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mLU/m); 6 weeks post bilateral oophorectomy with or without hysterectomy; post hysterectomy; or sterilized by tubal ligation
- A female of childbearing potential is defined as any woman physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means
•- Medically approved birth control methods may include: hormonal contraceptives, IUD, and double-barrier contraception. Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the subject ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Reliable contraception should be maintained throughout the study
8. Agreement to continue their current diet/exercise regimen and sulfonylurea, AGI, TZD, insulin, or metiglinide therapy throughout the duration of the study or to remain untreated if patient is not taking anti-diabetic therapy, unless otherwise instructed by the trial’s physician
9. Written informed consent to participate in the study and ability to comply with all study requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. FPG = 270 mg/dL (=15 mmol/L)
2. Pregnant or lactating female
3. A history of:
- Type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushing’s syndrome and acromegaly
- Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months
4. Patients that have been enrolled in a vildagliptin clinical trial or other DPP-4 inhibitor, GLP-1 mimetics (e.g. exenatide), GLP-1 analogues (e.g. liraglutide) studies within six months prior to visit 1
5. History of renal transplant at any time in the past
6. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study
7. Any current lower extremity diabetic skin ulcer
8. Patients taking TZDs with established peripheral edema
9. Congestive heart failure (NYHA class III-IV)
10. Any of the following within the past 6 months:
- myocardial infarction (if the visit 1 ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the patient can enter the clinical trial at the discretion of the investigator and/or local medical monitor);
- unstable angina
- coronary artery bypass surgery or percutaneous coronary intervention;
- stroke
11. Any of the following ECG abnormalities:
- Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation
- second degree AV block (Mobitz 1 and 2)
- third degree AV block
- prolonged QTc (> 500 ms)
12. Malignancy including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years
13. Liver disease such as cirrhosis or chronic active hepatitis B and C
15. Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study
16. Any of the following concomitant medications:
- any anti-diabetic therapy other than sulfonylureas, AGIs, TZDs, insulin, and metiglinides within 8 weeks prior to visit 1
- chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1
- treatment with class Ia, Ib and Ic or III anti-arrhythmics
- treatment with growth hormone or similar drugs
- treatment with probenecid
- treatment with any medication that is contraindicated in the renal impaired population (GFR < 50 mL/min/1.73 m2)
- treatment with any medication that is contraindicated in the use with sulfonylureas, AGIs, TZDs, insulin, and metiglinides
- use of other investigational drugs within 30 days or 5 half-lives of the drug at visit 1, which ever is longer, unless local health authority guidelines mandate a longer period
- treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e. cytostatic drugs)
17. Any of the following significant laboratory abnormalities:
- Clinically significant TSH outside of normal range at visit 1
- Clinically significant laboratory abnormalities at the opinion of the investigator
- Elevated fasting triglycerides > 500 mg/dL at visit 1, confirmed by a repeat measure within 3 working days
- ALT and/or AST > 2 x upper limit of normal (ULN) at visit 1, confirmed by a repeat measure within 3 working days
- Total bilirubin > 2 x ULN and/or direct bilirubin greater than the ULN at visit 1, confirmed by a repeat measure within 3 working days
- History of

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetes Type 2 together with moderate or severe renal insufficiency
MedDRA version: 12.1 Level: LLT Classification code 10067585 Term: Type 2 diabetes mellitus

Intervention(s)

Product Name: Vildagliptin
Product Code: LAF237
Pharmaceutical Form: Tablet
INN or Proposed INN: Vildagliptin
CAS Number: 274901-16-5
Current Sponsor code: LAF237A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - To explore the relationship between renal function and concentration levels of vildagliptin and its metabolites after repeated doses of vildagliptin (50 mg qd) in patients with T2DM and moderate or severe renal insufficiency.
- To explore the efficacy of vildagliptin (50 mg qd) vs. placebo in patients with T2DM and moderate or severe renal insufficiency by assessing the hemoglobin A1C (HbA1c) and fasting plasma glucose (FPG) reduction from baseline after 24 weeks of treatment.

Main Objective: To evaluate the safety and tolerability of vildagliptin (50 mg qd) vs. placebo in patients with T2DM and moderate or severe renal insufficiency over 24 weeks of treatment.

Primary end point(s): The variables for the primary objectives include treatment emergent adverse events (including hypoglycemia events and events of special interest), serious adverse events. Biochemistry and hematology laboratory test results, ECG findings, and vital signs/body weight will also be assessed.

Secondary ID(s)

CLAF237A23137

2007-003723-21-SE